Blood Product Safety

Indications

Whole blood is often divided into component parts for ease of storage and administration. These typically include red blood cells, platelets (thrombocytes), and plasma. Plasma can be further fractionated into cryoprecipitate (ie, cryoprecipitated antihemophilic factor) and many other clotting factor concentrates of variable purity.

The indications for whole blood and blood component transfusion include increasing hemoglobin and oxygenation of tissues, maintaining adequate blood volume to prevent ischemia and hypovolemic shock, and reconstituting platelets, coagulation factors, and other plasma proteins to a functional status. Hemoglobin and hematocrit, along with clinical symptoms of anemia, have traditionally been used as markers to determine the threshold for transfusing red blood cells. Hemoglobin levels of less than 10 g/dL or a hematocrit of less than 30% have traditionally been the laboratory indications for transfusion in the right clinical context. Recently, there has been increasing evidence that a lower threshold is associated with better outcomes and conservation of precious blood resources, even in critically ill populations.[2] There is some evidence that the transfusion "trigger" level may be slightly higher in certain conditions, such as sepsis with inadequate oxygen delivery, acute coronary syndrome with ischemia, and surgical hemorrhage, or in specific populations, such as the elderly. However, due to controlled trials and meta-analysis data, there has been a decrease in the use of liberal transfusion protocols.[3] Restrictive transfusion, even in patients with cardiovascular disease, acute illness, and traumatic brain injury, using a threshold of hemoglobin of 7 to 8 g/dL, has shown no increased risk of morbidity and mortality.[4][5] There is still variability globally in transfusion thresholds for particular patient populations.[6][7] Refer to specific topics on Indications for Red Blood Cell Transfusion for more information.

Platelets are typically given when patients have a low platelet count (thrombocytopenia) or have dysfunctional platelets, due to medications or other acquired or inherited lesions. Refer to specific topics on Indications for Platelet Transfusion for more information.

Plasma can be used to replace coagulation factors in specific coagulopathies (such as in liver disease when bleeding is present), reversal of warfarin effect (when coagulation concentrates are not available), and for the treatment of diseases such as thrombotic thrombocytopenic purpura. It is sometimes used as a replacement fluid in plasmapheresis and can be used for coagulation factor deficiencies where specific concentrates are not available. Refer to topics on Indications for Plasma Transfusion for more information.

Cryoprecipitate is a blood product derived from plasma. It can be used in emergencies as an alternative for supplying coagulation factors in inherited deficiencies such as von Willebrand disease and hemophilia A (but only when specific concentrates are unavailable). It can also be used to replenish fibrinogen in acquired coagulopathies such as disseminated intravascular coagulation and during trauma or childbirth.

Contraindications

Topics on Patient Blood Management outline the decision-making process required before administering a transfusion to a patient. Significant contraindications that merit consideration include the risk of transfusion in a patient who is volume overloaded or who has previously had a reaction to blood.[8] Another important consideration is to avoid transfusing blood without prior compatibility testing and antibody screening, unless it is an emergency.

Equipment

According to the American Association of Blood Banks, all blood bags and needles are sterile, used only once, and then discarded to prevent contamination from donor to donor that could later affect multiple recipients of transfusion. The equipment used for blood donation collection, including blood pressure monitors, scales, blood collection monitors/mixers, blood bag tube sealers, transportation boxes, and refrigerators, is routinely calibrated, cleaned, and serviced. The chairs and couches used in the area of blood donation should have cleanable surfaces, such as vinyl. Transport supplies and containers are also cleanable according to the World Health Organization guidelines. All blood bags should undergo routine inspection for sterility, expiration date, appearance, and any evidence of leakage or defects at the time of donation collection.

Personnel

Phlebotomy and blood collection should be performed by qualified personnel trained in blood donation procedures. Donation monitoring is under the overall responsibility of a medical practitioner or authorized personnel who can manage blood donor adverse reactions. Blood transfusions are also performed in patients with adequate oversight and under the supervision of a medical practitioner or other qualified healthcare professional. Real-time monitoring of patients during transfusion ensures that accurate information is available for the detection and work-up of suspected transfusion reactions. Laboratory technologists are trained and educated on the importance of appropriate testing for possible infectious agents before transfusion, blood group and compatibility, potential antibodies, and post-transfusion evaluations for hemolysis. Transfusion service personnel who are committed to following accepted guidelines and determining and auditing thresholds for transfusion have made significant contributions to blood product safety.

Preparation

To ensure the safety of blood products, several measures must be implemented during collection, manufacturing, and storage. The World Health Organization has supported a global initiative aimed at improving access to a safe and sufficient blood supply. Once collected, the blood is tested for donor blood type and screened for any clinically significant donor antibodies. The collecting facility typically holds the blood until the appropriate preparation and routine screening for potential transfusion-transmitted infections is complete. When all legal and industry standards have been met and the product is ready for transfusion, then it is "labelled" (ie, identified as ready for use).

The widespread prioritization of testing for transfusion-transmitted infections has significantly improved blood product safety worldwide. A summary of information on countries that responded to questionnaires about their specific policies and guidelines regarding the testing of donor blood is presented in Figure 2, according to the World Health Organization's 2016 Global Status Report on Blood Safety and Availability. The survey found that the majority of responding countries had policies for testing the most common and clinically relevant transfusion-transmitted infections, including HIV, hepatitis C, hepatitis B, and syphilis. Eighteen nations in Latin America reported having a policy for testing all blood donations for Trypanosoma cruzi along with twelve countries implementing selective testing for T cruzi in donors who have traveled to high-risk areas or have defined risk factors. Thirty-seven nations reported having a policy of testing all blood donations for antibodies to human T-lymphotropic virus (HTLV-I/II), while 7 countries reported conducting selective additional testing for new donors.

Following the collection of a blood donation, several procedures can be performed during the preparation of the blood for transfusion. Leukodepletion is a procedure that reduces the number of white blood cells in a blood product, thereby decreasing the risk of febrile reactions, HLA sensitization, and CMV transmission. Bacterial contamination testing of platelets can be performed before transfusion to avoid septic transfusion reactions. Plasma fractionation provides the opportunity to derive specific factor concentrates and intravenous immune globulin. Gamma irradiation of blood products can be performed to reduce the risk of transfusion-associated graft-versus-host disease, which is nearly always fatal.[9] Plasma reduction or washing of blood products limits the amount of plasma within a cellular blood product, which reduces the risk of allergic transfusion reactions or the effects of incompatible type A, B, AB, or O (ABO) antibodies. Volume reduction can also be used to reduce excess potassium and cytokines, which can cause electrolyte imbalance and febrile non-hemolytic transfusion reactions, respectively.[10][11] Blood typing and screening for donor and recipient alloantibodies, as well as compatibility testing, are also crucial aspects of preparing for a transfusion. Screening donated blood for alloantibodies is essential in preventing hemolytic transfusion reactions in recipients.

The new frontier in blood product safety is pathogen reduction (pathogen inactivation), which is a broad term for various methodologies applied to blood products post-collection to reduce the risk of transmission of infectious agents.[12] Many of these technologies protect various classes of infectious agents, including viruses, bacteria, and parasites. Another potential benefit is that some of these technologies also inactivate donor white blood cells, which has allowed some to gain approval for the prevention of transfusion-associated graft-versus-host disease (as an alternative to irradiation). Pathogen reduction procedures are currently approved in some countries for platelet and plasma transfusions.[13] These novel technologies can increase the shelf life of platelets and decrease the incidence of adverse transfusion reactions and bacterial contamination. These approaches are becoming increasingly common in practice and are expected to help improve blood product safety profiles.[14]

Technique or Treatment

An important aspect of the donation process is the donor-screening questionnaire. Donor recruitment represents a crucial frontline mechanism for ensuring blood safety. The highest rates of transfusion-transmitted infections are found among donors who receive monetary compensation, while the lowest rates of infection are observed among unpaid volunteer donors.[15][16] "Replacement" and "family" donors are relied on in some countries, but these are not considered as safe as true altruistic, unpaid volunteers. A great reduction in the risk of transfusion-transmitted HIV, HCV, HBV, and syphilis infections has transpired with the initial donor screening questions and improved testing, including serology and nucleic acid amplification testing.[17][18] According to the United States Food and Drug Administration, highly sensitive donor screening questionnaires designed to exclude high-risk donors for the transmission of infections exclude an estimated 90% of potentially infectious donors from blood donation. Donors who have incentives to donate (such as monetary gain or wanting to help a friend) may not be completely truthful during screening.

Individual blood service organizations may have subtle variations in collection procedures, but the World Health Organization provides guidelines on the proper technique for venipuncture for blood donation. These standardize the process and are in place to prevent transfusion-transmitted infections. A safe collection is paramount to ensure that blood products remain safe throughout the collection, storage, and transfusion process.

Bacterial contaminants typically originate from normal skin flora; therefore, proper antiseptic technique is required before collection. The recommended procedure by the World Health Organization involves applying a combination of 2% chlorhexidine gluconate and 70% isopropyl alcohol for 30 seconds, followed by a 30-second drying period. A closed collection system (not open to the air) is used to ensure sterility. This procedure involves an anticoagulant-containing collection bag with an intrinsically attached tube and needle. The first 15 to 20 mL of blood is collected in a diversion bag so that, in the event of possible skin contamination, the initial blood collected can be used for laboratory testing and not transfused. This diverted blood is the most likely to be contaminated by skin flora and the skin plug (created by the needle); therefore, removing this from the transfusion reduces contamination risk.[19] Blood volumes collected vary by the technique used. According to the World Health Organization, approximately 350 milliliters of blood are collected for whole blood transfusion. For the production of packed red cells, fresh frozen plasma, and platelet concentrates in double or triple bags, a volume of 450 milliliters is required. The volume is selected to prevent donor transfusion-associated anemia and other adverse events.

Blood donations can be separated into 4 main components (red blood cells, platelets, plasma, and cryoprecipitate) or left as whole blood. Once the blood has undergone processing, it is stored at an appropriate temperature (often between +2°C and +6°C).[20][21] Platelets and fresh frozen plasma (FFP) require preparation within 8 hours of collection. Platelets are stored at room temperature and with agitation, typically for 5 days, unless additional shelf-life-extending mechanisms are employed.[22] Depending on the national regulations, fresh frozen plasma can be stored at -18°C for 1 year, -25°C for 36 months, or at -65°C for up to 7 years.[20] Many countries are transitioning to using "plasma" instead of FFP, which allows for up to 24 hours after collection before processing and freezing are required. The temperature and duration of storage depend on blood service guidelines and storage capabilities of individual institutions. Sterility is maintained throughout the processing and storage steps to prevent contamination. Blood units are unavailable for transfusion until undergoing appropriate testing, including ABO and Rh blood group typing and antibody screening, as well as serologic testing for transfusion-transmitted infections.

Complications

According to the World Health Organization Guidelines on Drawing Blood: Best Practices in Phlebotomy, complications of blood donation include (from most likely to least likely) a hematoma, vasovagal reaction or syncope, delayed syncope, arterial puncture, and nerve damage. Complications of blood transfusion include transfusion reactions and transfusion-transmitted infections.[23] The risk of transfusion-transmitted infection has fallen very low in high-income countries, with a risk of less than 1 in 1 million for most of the concerning pathogens, such as HIV, HCV, and HBV.[17] Donor screening techniques that select blood from only low-risk donors have had the most significant impact on reducing pathogens transmitted through transfusion. Exclusion criteria include medical history, high-risk behaviors, physical examination findings, geographic, and travel exclusions. There are also serologic and nucleic acid tests that have reduced the risk of transmission by infectious agents. It is worth noting that laboratory testing may not detect all pathogens due to a small number of false-negative tests. Therefore, screening questionnaires remain vital to eliminate high-risk donors. Donating blood should never be seen as an easy way to find out about the infectious disease status of at-risk persons.

Although the risk of transfusion-transmitted infection has decreased substantially, bacterial contamination in platelets stored at room temperature is still a concern for potential septic transfusion reactions. Bacterial contamination is typically caused by commensal bacteria normally found on the skin of donors or by transient bacteremia in donors. Another growing concern is the transmission of emerging pathogens through transfusion, such as the Zika virus and babesiosis. As the risk of infectious complications has decreased, noninfectious transfusion complications have become the primary area of concern and focus for improvement. The efforts focused on detecting, recognizing, and reporting transfusion-related adverse events have improved the safety of blood and blood component transfusions. Transfusion reactions that can occur with blood transfusion range from life-threatening to circumstances in which transfusion can continue once the cause of the reaction is determined (eg, simple allergic reaction). The most common reactions include the following:

• Transfusion-associated circulatory overload
• Transfusion-related acute lung injury (TRALI)
• Transfusion-associated dyspnea
• Simple allergic reaction
• Anaphylactic reaction
• Hypotensive transfusion reaction
• Febrile non-hemolytic transfusion reaction
• Acute hemolytic transfusion reaction
• Delayed hemolytic transfusion reaction
• Delayed serologic transfusion reaction
• Transfusion-associated graft vs. host disease
• Post-transfusion purpura
• Transfusion-transmitted infection [23]

With efforts to reduce TRALI, transfusion-associated circulatory overload has been an emerging concern for morbidity and mortality in patients receiving blood transfusions.[24] Improved awareness around transfusion reactions and their etiology has improved blood product safety.[25][26][27][28] Estimated incidence rates for several of the complications of transfusion and specific transfusion-related adverse events are shown in Figure 3.[29][30][31][32]

Clinical Significance

Blood transfusion is one of the most common clinical procedures. Blood product safety is a crucial aspect of quality healthcare received worldwide. Approximately 112 million units of blood are collected globally every year, according to the World Health Organization. Nearly 14 million units of blood (whole blood and packed red blood cells) are transfused annually worldwide.[33] The American Red Cross estimates that approximately 36,000 units of blood are needed daily in the United States. Blood transfusion is a lifesaving procedure that occurs daily in hospitals and clinics worldwide.

There has been a push to move away from blood transfusions and to require more stringent guidelines for the use of blood and blood products. According to the National Blood Collection and Utilization Survey, there has been a steady decline in the rate of transfusions in the USA, without a significant adverse effect on morbidity and mortality.[34] This finding is likely due to advances in surgical management of patients as well as policies for judicious use of blood products. This may also be due to evidence that liberal usage of blood products has correlated with poor patient outcomes.[35] Several studies have found a correlation between perioperative transfusion and increased morbidity and mortality, as well as a longer length of stay during hospitalizations.[36][37][38] Considering these findings, clinically restrictive transfusion protocols have shaped more recent guidelines in many countries.[39][40] However, there remains a delicate balance between treating symptomatic anemia and preventing transfusion-related adverse events.[41][42]

Transfusion reactions continue to be a significant cause of increased hospital stays and adverse patient outcomes. Transfusion reactions occur in approximately 1 in every 100 transfusions, making them an important clinical consideration for patients receiving transfusions.[43] Considering the number of transfusions that occur worldwide, blood product safety is a crucial aspect of enhancing patient care. The education of clinical staff surrounding signs and symptoms of a transfusion reaction, as well as efforts aimed at the judicious use of blood products, has improved the safety of transfusion.[23][33] Blood product transfusion is a life-saving procedure that has significantly improved patient outcomes. New efforts to restrict the use of blood products to patients with genuine medical need, improve the collection and storage of blood products, and develop alternatives to transfusion promise increased safety for this lifesaving procedure.

Enhancing Healthcare Team Outcomes

Nurses, trained technical staff, and phlebotomists are involved in collecting, screening, modifying blood, and monitoring blood donors throughout the donation process in a safe and standardized manner. Laboratory personnel play a crucial role in ensuring the safe testing and handling of blood products. Nurses and laboratory technologists play a pivotal role in verifying patient information and ensuring that the correct blood product gets to the right patient at the right time. Nurses who monitor and document patient vital signs and symptoms during blood transfusions play a crucial role in ensuring patient safety and in identifying possible transfusion reactions. Pharmacists and clinicians assist patients with known allergic reactions or febrile non-hemolytic transfusion reactions during blood transfusions. In the case of mild allergic transfusion reactions, medication is provided to help alleviate the reaction, allowing the transfusion to resume. Physicians work closely with the blood bank at their institution to coordinate care and provide blood in a timely and sensitive manner. Communication on multiple levels of an interprofessional team caring for patients is critical for this life-saving procedure to be effective and safe for patients. Transfusion safety officers and related professionals play a crucial role in monitoring blood transfusion criteria and physician ordering of blood products, thereby contributing to transfusion mindfulness and hemovigilance efforts.[44][45]